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A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.

https://arctichealth.org/en/permalink/ahliterature186025
Source
J Bone Miner Res. 2003 Apr;18(4):723-9
Publication Type
Article
Date
Apr-2003
Author
Bo Abrahamsen
Jonna Skov Madsen
Charlotte Landbo Tofteng
Lis Stilgren
Else Marie Bladbjerg
Søren Risom Kristensen
Kim Brixen
Leif Mosekilde
Author Affiliation
Department of Endocrinology, Odense University Hospital, Odense, Denmark. B.abrahamsen@dadlnet.dk
Source
J Bone Miner Res. 2003 Apr;18(4):723-9
Date
Apr-2003
Language
English
Publication Type
Article
Keywords
Alleles
Bone Density - genetics - physiology
Denmark - epidemiology
Estrogen Replacement Therapy
Female
Fractures, Bone - enzymology - epidemiology - genetics
Gene Frequency
Genotype
Humans
Longitudinal Studies
Methylenetetrahydrofolate Reductase (NADPH2) - genetics - physiology
Middle Aged
Osteoporosis, Postmenopausal - enzymology - genetics - prevention & control
Polymorphism, Genetic
Proportional Hazards Models
Prospective Studies
Risk factors
Abstract
A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p
PubMed ID
12674333 View in PubMed
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Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.

https://arctichealth.org/en/permalink/ahliterature90229
Source
Hum Mol Genet. 2009 Apr 15;18(8):1510-7
Publication Type
Article
Date
Apr-15-2009
Author
Timpson Nicholas J
Tobias Jon H
Richards J Brent
Soranzo Nicole
Duncan Emma L
Sims Anne-Marie
Whittaker Pamela
Kumanduri Vasudev
Zhai Guangju
Glaser Beate
Eisman John
Jones Graeme
Nicholson Geoff
Prince Richard
Seeman Ego
Spector Tim D
Brown Matthew A
Peltonen Leena
Smith George Davey
Deloukas Panos
Evans David M
Author Affiliation
MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, UK.
Source
Hum Mol Genet. 2009 Apr 15;18(8):1510-7
Date
Apr-15-2009
Language
English
Publication Type
Article
Keywords
Aged
Body Height - genetics
Bone Density - genetics
Child
Chromosomes, Human, Pair 12
Genome-Wide Association Study
Humans
Longitudinal Studies
Middle Aged
Polymorphism, Single Nucleotide
Transcription Factors - genetics
Abstract
Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We compared results with a scan of 134 adults with high or low hip BMD. We identified associations with BMD in an area of chromosome 12 containing the Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast differentiation (ALSPAC: P = 5.8 x 10(-4); Australia: P = 3.7 x 10(-4)). This region has previously shown evidence of association with adult hip and lumbar spine BMD in an Icelandic population, as well as nominal association in a UK population. A meta-analysis of these existing studies revealed strong association between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 x 10(-11)). In light of these findings, we genotyped a further 3692 individuals from ALSPAC who had whole body BMD and confirmed the association in children as well (P = 5.4 x 10(-5)). Moreover, all SNPs were related to height in ALSPAC children, but not weight or body mass index, and when height was included as a covariate in the regression equation, the association with total body BMD was attenuated. We conclude that genetic variants in the region of Osterix are associated with BMD in children and adults probably through primary effects on growth.
PubMed ID
19181680 View in PubMed
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Interleukin-6 gene polymorphism is related to bone mineral density during and after puberty in healthy white males: a cross-sectional and longitudinal study.

https://arctichealth.org/en/permalink/ahliterature49914
Source
J Bone Miner Res. 2000 Oct;15(10):1944-9
Publication Type
Article
Date
Oct-2000
Author
M. Lorentzon
R. Lorentzon
P. Nordström
Author Affiliation
Department of Surgical and Perioperative Sciences, Umeå University, Sweden.
Source
J Bone Miner Res. 2000 Oct;15(10):1944-9
Date
Oct-2000
Language
English
Publication Type
Article
Keywords
Adolescent
Body Height
Body Weight
Bone Density - genetics
Cross-Sectional Studies
European Continental Ancestry Group - genetics
Exercise
Genotype
Humans
Interleukin-6 - genetics
Longitudinal Studies
Male
Polymorphism, Single Nucleotide - genetics
Promoter Regions (Genetics) - genetics
Puberty - physiology
Research Support, Non-U.S. Gov't
Statistics
Sweden
Abstract
Bone mineral density (BMD) is under strong genetic control and is the major determinant of fracture risk. The cytokine interleukin-6 (IL-6) is an important regulator of bone metabolism and is involved in mediating the effects of androgens and estrogens on bone. Recently, a G/C polymorphism in position -174 of the IL-6 gene promoter was found. We investigated this genetic polymorphism in relation to BMD during late puberty and to peak bone mass, in healthy white males. We identified the IL-6 genotypes (GG, GC, and CC) in 90 boys, age 16.9 +/- 0.3 years (mean +/- SD), using polymerase chain reaction (PCR). BMD (g/cm2) at the femoral neck, lumbar spine, and total body was measured using dual energy X-ray absorptiometry. The volumetric BMD (vBMD; mg/cm3) of the lumbar spine was estimated. Differences in BMD in relation to the genotypes were calculated using analysis of variance (ANOVA). Subjects with the CC genotype had 7.9% higher BMD of the femoral neck (p = 0.03), 7.0% higher BMD of the lumbar spine (p GG; p = 0.03), humerus BMD (CC > GG; p GG; p = 0.01), spine BMD (CC > GG; p = 0.01), and spine vBMD (CC > GG; p = 0.008). At age 19.3 +/- 0.7 years (mean +/- SD; 88 men) the IL-6 genotypes were still independent predictors for total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p = 0.03), spine BMD (CC > GG; p = 0.02), and spine vBMD (CC > GG; p = 0.003), while the IL-6 genotypes were not related to the increase in bone density seen after 2 years. We have shown that polymorphism of the IL-6 gene is an independent predictor of BMD during late puberty and of peak bone mass in healthy white men.
PubMed ID
11028446 View in PubMed
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Lack of influence of collagen type Ialpha1 Sp1 binding site polymorphism on the rate of bone loss in a cohort of postmenopausal danish women followed for 18 years.

https://arctichealth.org/en/permalink/ahliterature198522
Source
Calcif Tissue Int. 2000 Jun;66(6):409-13
Publication Type
Article
Date
Jun-2000
Author
A. Heegaard
H L Jorgensen
A W Vestergaard
C. Hassager
S H Ralston
Author Affiliation
Center for Clinical & Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark.
Source
Calcif Tissue Int. 2000 Jun;66(6):409-13
Date
Jun-2000
Language
English
Publication Type
Article
Keywords
Absorptiometry, Photon
Binding Sites
Bone Density - genetics
Bone Resorption - blood
Collagen - genetics - urine
Denmark
Female
Femur - radiography
Follow-Up Studies
Forearm - radiography
Humans
Longitudinal Studies
Middle Aged
Osteocalcin - blood
Osteoporosis, Postmenopausal - genetics - physiopathology - radiography
Polymerase Chain Reaction
Polymorphism, Genetic - genetics
Spine - radiography
Time Factors
Abstract
A polymorphism in an Sp1 site in the collagen Ialpha1 (COLIA1) gene has recently been identified and the Ss and ss genotypes were shown to be potentially important determinants of low bone mass in postmenopausal women. Additionally, in a Dutch population, the association of the COLIA1 polymorphism with low bone mineral density (BMD) was more pronounced with increasing age, suggesting a genotype effect on the rate of bone loss. We have investigated the relationship between the COLIA1 Sp1 polymorphism and the rate of bone loss in a longitudinal study with a total of 133 postmenopausal women followed for 18 years. The frequencies of the genotypes were SS 70.7%, Ss 27.8%, ss 1.5% and were in Hardy-Weinberg equilibrium. No association of the COLIA1 genotype with rate of bone loss was detected and there was no difference between the genotype groups with respect to BMD at the femoral neck or lumbar spine. Women with the Ss or ss genotypes, who have been postulated to have low BMD, had even higher BMD at the lower forearm than women with the SS genotype. The levels of serum osteocalcin and urinary collagen type I degradation products were not found to be associated with the COLIA1 Sp1 polymorphism. In conclusion, this study does not support the hypothesis that the Ss COLIA1 genotype predisposes women to increased rate of bone loss or low BMD. However, because of a low absolute number of the ss genotype, it was not possible to reach a conclusion on this particular genotype with regard to an association with low BMD or rate of bone loss.
PubMed ID
10821875 View in PubMed
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No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women.

https://arctichealth.org/en/permalink/ahliterature199108
Source
Bone. 2000 Feb;26(2):111-6
Publication Type
Article
Date
Feb-2000
Author
Y Z Bagger
H L Jørgensen
A M Heegaard
L. Bayer
L. Hansen
C. Hassager
Author Affiliation
Center for Clinical and Basic Research, Ballerup, Denmark. yb@ccbr.dk
Source
Bone. 2000 Feb;26(2):111-6
Date
Feb-2000
Language
English
Publication Type
Article
Keywords
Aged
Alleles
Base Sequence
Bone Density - genetics - physiology
Cross-Sectional Studies
DNA Primers - genetics
Denmark
Estrogen Replacement Therapy
Female
Genotype
Humans
Longitudinal Studies
Middle Aged
Osteoporosis, Postmenopausal - genetics - metabolism
Polymorphism, Restriction Fragment Length
Receptors, Estrogen - genetics
Abstract
The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69 years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate of bone loss either in the hip and spine over 6 years, or in the lower forearm over 18 years. In conclusion, we could not demonstrate any major effect of the ER gene polymorphisms on BMD or rate of bone loss in healthy postmenopausal Danish women.
PubMed ID
10678404 View in PubMed
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Vitamin D receptor alleles do not predict bone mineral density or bone loss in Danish perimenopausal women.

https://arctichealth.org/en/permalink/ahliterature205583
Source
Bone. 1998 May;22(5):571-5
Publication Type
Article
Date
May-1998
Author
T S Hansen
B. Abrahamsen
F L Henriksen
A P Hermann
L B Jensen
M. Hørder
J. Gram
Author Affiliation
Department of Clinical Biochemistry and Clinical Genetics, Odense University Hospital, Denmark.
Source
Bone. 1998 May;22(5):571-5
Date
May-1998
Language
English
Publication Type
Article
Keywords
Absorptiometry, Photon
Alkaline Phosphatase - blood
Alleles
Bone Density - genetics - physiology
Bone Development - genetics - physiology
Calcitriol - blood
Calcium - metabolism
Cohort Studies
Denmark
Female
Femur - physiology
Follow-Up Studies
Genotype
Humans
Hydroxyproline - urine
Longitudinal Studies
Lumbar Vertebrae - physiology
Middle Aged
Osteocalcin - blood
Osteoporosis, Postmenopausal - genetics
Premenopause - physiology
Receptors, Calcitriol - genetics - physiology
Abstract
A BsmI restriction enzyme polymorphism in the vitamin D receptor (VDR) gene has been reported to be associated with bone mineral density (BMD) and bone turnover. However, findings in other studies suggest the presence of considerable interaction by race, body size, and environmental factors. Therefore, we VDR BsmI genotyped 200 healthy perimenopausal Danish white women (mean age 50.8 years, mean calcium intake 900 mg/day) in a comprehensive, longitudinal, community-based population study. Bone loss was assessed by dual-energy X-ray absorptiometry (DXA) using cross-calibrated Hologic QDR-1000W and QDR-2000 densitometers, with a mean follow-up period of 4 years (range 1-5 years). Despite a distribution of genotypes similar to that of other white populations (28% bb, 49% Bb, 23% BB), VDR genotypes were not associated with lumbar or femoral baseline BMD, subsequent bone loss rates, or biochemical markers of bone metabolism (bone-specific alkaline phosphatase, urinary hydroxyproline, and serum osteocalcin). Controlling for body size, calcium intake, and serum levels of 25-hydroxyvitamin D3 [25(OH)D3] did not alter this finding. The possible existence of a threshold effect was subsequently investigated by restricting analysis to women with low serum 25(OH)D3 levels or low calcium intake. VDR BsmI genotypes showed no significant impact on bone density or bone loss in healthy Danish early postmenopausal women, even when allowance was made for calcium intake, serum 25(OH)D3, and body size.
PubMed ID
9600794 View in PubMed
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6 records – page 1 of 1.